e-Cigarettes, also known as electronic nicotine delivery systems (ENDS), are a rapidly growing nicotine delivery product with millions of users in the United States and worldwide. All e-cigarettes have common features: a battery; a tank containing propylene glycol or vegetable glycerin, flavoring agents, and nicotine; a microprocessor; an activating button; and, in some, a variable voltage heating element. The heating element vaporizes the solution producing liquid aerosol droplets containing nicotine. The amount of nicotine inhaled is controlled by the user by varying the voltage. There is little doubt that e-cigarettes are safer than tobacco cigarettes because they lack tobacco and combustion. However, the safety of e-cigarettes per se requires evaluation, particularly in view of recent reports that they may generate unacceptable levels of the human carcinogen formaldehyde, and our preliminary data indicating that levels of urinary biomarkers of oxidative damage and inflammation ? the F2-isoprostane 8-iso-PGF2? and the prostaglandin E2 metabolite PGEM - are the same in e- cigarette users as in cigarette smokers. Therefore, we will test the hypothesis that e-cigarette use leads to formaldehyde-DNA adducts and elevated exposure to other carbonyls, and to similar levels of oxidative damage and inflammation as in smokers, and will assess toxicant and carcinogen exposure in e-cigarette users, smokers, and non-smokers. Our specific aims are: 1. Quantify exogenous [13CD2]formaldehyde-DNA adducts and unlabeled endogenous formaldehyde-DNA adducts in tissues of rats exposed to vapor generated from e-liquids containing [1-13CD2]propylene glycol. 2. Using samples from a prior study in which smokers stopped smoking for 12 weeks, determine the time course of decreases in formaldehyde-DNA adducts in leukocytes, and 8-iso-PGF-2? and PGEM in urine.3. Recruit 134 e-cigarette tank system users, 134 smokers, and 134 non-users of any e-cigarette or tobacco product and compare levels of formaldehyde, diacetyl, and other carbonyl compounds in saliva (before and after puffing in the e-cigarette users and smokers), formaldehyde-DNA adducts in oral cells and leukocytes, 8-iso-PGF-2? and PGEM in urine, the serum biomarker of inflammation C-reactive protein, as well as a panel of urinary toxicant and carcinogen biomarkers, sampled monthly for 6 months. Only e-cigarette users who have not smoked a tobacco cigarette for the amount of time determined to be necessary for clearance of biomarkers to non-smoker levels in Specific Aim 2 will be enrolled, and this group will include e-cigarette users who operate their devices at predominantly high and low voltages (above and below 4V) as well as some individuals who will vary the voltage of their e-cigarette system.Collectively, the results of this study will critically test our hypothesis and provide important data on the potential risks of e-cigarette use with respect to the human carcinogen formaldehyde and other carbonyl compounds, oxidative damage and inflammation, and exposure to a panel of toxicants and carcinogens.